title: RRAS: A key regulator and an important prognostic biomarker in biliary atresia.
abstract: OBJECTIVE
  To characterize the differentially expressed gene profiles in livers from biliary atresia (BA) patients including, ascertain genes, functional categories and pathways that play a central role in the pathogenesis of BA, and identify the novel prognostic markers for BA.
  
  
  METHODS
  Liver tissue samples from control patients, neonatal cholestasis patients, and BA patients at the age of < 60 d, 60-90 d, and > 90 d were pooled for DNA microarray analysis. Bioinformatics analysis was performed using, series test cluster of gene ontology, and Pathway-Finder software. Reverse-transcription polymerase chain reaction was performed to confirm changes in selected genes. Relation between RRAS gene expression and prognosis of 40 BA patients was analyzed in a 2-year follow-up study.
  
  
  RESULTS
  The 4 identified significant gene expression profiles could confidently separate BA liver tissue from normal and other diseased liver tissues. The included genes were mainly involved in inflammation response and reconstruction of cellular matrix. The significant pathways associated with BA were primarily involved in autoimmune response, activation of T lymphocytes and its related cytokines. The RRAS, POMC, SLC26A6 and STX3 genes were important regulatory modules in pathogenesis of BA. The expression of RRAS was negatively correlated with the elimination rate of jaundice and positively correlated with the occurrence rate of cholangitis.
  
  
  CONCLUSIONS
  Autoimmune response mediated by T lymphocytes may play a vital role in the pathogenesis of BA. The RRAS gene is an important regulatory module in the pathogenesis of BA, which may serve as a novel prognostic marker for BA.
authors.affiliation: Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Chun
authors.initials: C
authors.lastname: Shen
authors.forename: Shan
authors.initials: S
authors.lastname: Zheng
mesh_terms: D001656:Biliary Atresia / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology / Q000502:physiology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C085929:RRAS protein, human; D018631:ras Proteins